The present invention relates to a medicament for neurodegenerative diseases comprising zonisamide or an alkali metal salt thereof as the active ingredient.
Zonisamide [chemical name: 3-sulfamoylmethyl-1,2-benzisoxazole or 1,2-benzisoxazole-3-methanesulfonamide; see, for example, Merck Index, 12th Ed., 10323 (1996)] has been used as an antiepileptic agent in the treatment or prevention of various seizures in Japan, South Korea, etc. JP-B-60-33114, JP-B-61-59288 and U.S. Pat. No. 4,172,896 disclose processes for preparing zonisamide and the utility thereof as an antiepileptic agent. Further, JP-B-7-84384 and U.S. Pat. No. 5,128,354 also disclose the utility of zonisamide as a medicament for ischemic brain damage.
With developing into an aging society, the number of patients suffering from neurodegenerative diseases such as Parkinson""s disease is increasing. Parkinson""s disease is a progressive and tragic disease by which coordinated movement of patient is disturbed, and the movement of patient becomes slow with the lapse of time, and finally, rigidity or tremor of arms and legs develop. It has been known that said disease is caused by depletion of striatum dopamine due to rhexis and loss of dopamine-producing neurons in nigro-striatal.
Incidentally, a striatal dopamine-depleted animal, which is prepared by administering 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (hereinafter, referred to as xe2x80x9cMPTPxe2x80x9d) to a C57 black mouse, has been widely used as an animal model for Parkinson""s disease. Life Sci., 54, 245 (1994) discloses that antiepileptic agents: lamotrigine [chemical name: 3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine] and phenytoin show an inhibitory effect on dopamine depletion induced by MPTP, while carbamazepine does not show such effect. However, in the experiments of said literature, MPTP hydrochloride was subcutaneously injected at a dose of 15 mg/kg only once to C57 black mice, and therefore said mice are not necessarily suitable as an animal model for Parkinson""s disease.
In the current medication of Parkinson""s disease, there are used dopamine replenishing agents (e.g., levodopa alone, or a combination product or combined therapy of levodopa and carbidopa), dopaminergic agonists (e.g., bromocriptine or terguride), dopamine releasing agents (e.g., amantadine), anticholinergic agents (e.g., biperiden or trihexyphenidyl), monoamine oxidase type B (MAO-B) inhibitors (e.g., selegiline), etc. However, these agents are not necessarily satisfactory from the viewpoint of efficacy and side effects, and it has been expected to develop a novel effective medicament.
The present inventors have found that zonisamide and an alkali metal salt thereof exhibit an extremely potent inhibitory effect on the MPTP-induced dopaminergic neurodegeneration, and have accomplished the present invention.
An object of the present invention is to provide a medicament for the treatment of neurodegenerative diseases comprising zonisamide or an alkali metal salt thereof as an active ingredient.
Another object of the present invention is to provide use of zonisamide or an alkali metal salt thereof for the manufacture of a medicament for neurodegenerative diseases.
A further object of the present invention is to provide a method for the prevention and/or treatment of neurodegenerative diseases in a mammal (including human), which comprises administering an effective amount of zonisamide or an alkali metal salt thereof to said mammal in need of such prevention and/or treatment.